In our office we are starting to get a lot of questions about the new RSV vaccines that have finally arrived, from people on both sides of the vaccine debate and along the continuum in between. RFK Jr. is not adding meaningful facts to the discussion. And finding sufficient time to provide thorough answers at the end of a visit is tough, while not devolving into political debates. So here’s a deep dive on how I would like to respond! The most common question this week is simply: should I get it? The CDC has outsourced a lot of that answer to primary care physicians, and presumably pharmacists, as there is no automatic answer for everyone. So here are some decision points I synthesized and investigated. Feel free to pass this on, and then hash it out with a professional who knows your unique medical history and problems.
~ Do I need to be worried about RSV?
Respiratory Syncytial Virus in adults typically presents with a cough, sore throat, congestion, runny nose, headache, mild fevers, and fatigue. It’s one of 200+ pathogens that can cause what we think of as a “bad cold.” RSV can sometimes progress to pneumonia, bronchitis, and other lower respiratory infections. Babies, the elderly, adults with certain chronic diseases (listed here), weakened immune systems, and those living in nursing homes or long-term care facilities are at higher risk for severe disease. This post will focus on the over 65 crowd.
For adults over the age of 65, RSV season in the U.S. results in about 60,000 - 160,000 hospitalizations, and 6,000-10,000 deaths. That’s out of a population of about 56 million. In terms of the impact on adults in this age group, RSV runs a close second to influenza.
The CDC’s Advisory Committee on Immunization Practices recommended in June that any persons over age 60 should be able to get the RSV vaccine after shared decision making. They note that “RSV vaccines have demonstrated moderate to high efficacy in preventing RSV-associated lower respiratory tract disease and have the potential to prevent substantial morbidity and mortality among older adults.”
Overall, if you’re over 60, and the prospect of getting a “bad cold” that might lead to bronchitis, pneumonia, hospitalization or worse seems likely, then getting the RSV vaccine is worth the small risks.
As new vaccines, these appear quite well-tolerated overall… but with a possible catch regarding a condition called GBS. Read on.
~ Good relative risk reductions, with eye popping percentages 😃 😳
In terms of relative risk reductions, these two vaccines are quite similar. They were not compared head-to-head, so the small differences in percentages between them cannot be used to say one is better than the other… they look pretty equivalent at this time.
For the Pfizer RSV vaccine called Abrysvo, studied in 34,000 patients:
90% effective against severe lower respiratory infections like pneumonia and bronchitis caused by RSV
Protection remained high at 79% through the second year after the shot
67% effective against RSV infection of any severity, including mild illness
For the GSK RSV vaccine called Arexvy, studied in 25,000 patients:
94% effective against severe lower respiratory infections like pneumonia and bronchitis caused by RSV, and 82% effective at preventing less severe cases
70% effective against RSV infection of any severity, including mild illness
And broken down by season: overall efficacy of 82% against lower respiratory tract disease during the first season, 77% for mid-season, and 67% over two seasons. Against severe disease, efficacy was 94.1% during the first season, 84% at mid-season, and 79% over two seasons.
Unfortunately these vaccines were not studied in enough high risk patients and elderly patients over 75-80 years of age to perform a subgroup analysis. For example, the average age of the patients in the Pfizer study was 68. We will have to see this year if the vaccines do particularly well for the >80 y.o. population, and hopefully without higher adverse events.
~ Less convincing absolute risk reductions, with eye popping numbers-needed-to-treat 😐 😳
One statistical issue I’ve written about before is the disconnect between relative risk reductions that sound impressive, and corresponding absolute risk reductions that deflate the hype. We just saw numbers like “95% vaccine effectiveness,” but what does that mean on an absolute basis?
Here’s how Mark Ebell, M.D., a professor and editor of Essential Evidence Plus, breaks it down for the Pfizer study:
The absolute number of infections prevented was also reported using a different metric by the Pfizer study authors. They measured cases in person-years. Person years take into account both the number of people in the study and the amount of time each person spends in the study. For example, a study that follows 1,000 people for one year would contain 1,000 person-years of data. You don’t have to understand this completely to get the gist. From the original study published in the New England Journal of Medicine:
17,215 participants received the Pfizer RSV vaccine, while 17,069 participants received placebo. RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) versus 33 participants in the placebo group (3.58 cases per 1000 person-years of observation).
This equates to that vaccine efficacy 67%, which I admit still sounds more impressive in the relative risk section above.
Neither the Pfizer nor the GSK study had enough patients enrolled to prove that these vaccines reduced hospitalizations or death. For example, in the Pfizer study there was 1 death from RSV disease in the vaccinated group, versus 3 in the placebo group (not statistically significant). This is not surprising.
Recall that the upper limit estimate for deaths from RSV in people over age 65 in the U.S. was 10,000 per year out of a total population of 56 million seniors.
10,000 divided by 56 million means 0.02% expected to die of RSV per year.
That’s 2 people per 10,000 on a bad year, right?
[This article was originally posted on my Substack called EXAMINED. There I present vital and overlooked ideas your family doc might share, if only we had more time. A little politics trickle in, but I try to keep it non-partisan, the way science should be. New sign ups always welcomed☺️]
~ The most concerning possible side effects right now seem to be neurological
Overall these vaccines were very well tolerated, on par with other approved vaccines. Common side effects like sore arm, fatigue, etc. were predictable. However…
Guillain-Barré syndrome (GBS) is a condition in which the immune system is triggered to attack nerves. This can lead to muscle weakness and even paralysis. While most people improve and recover, some others are left with permanent nerve damage. GBS can be triggered by viral and bacterial infections. It can also rarely be triggered by some vaccinations like the flu shot. It is estimated that the flu shot causes 1 or 2 extra cases of GBS per million vaccinations, while actual influenza disease causes several times that.
In the Pfizer RSV study there were 3 cases of GBS.
The background rate of GBS in the general population is 1-3 cases per 100,000 people, so we are potentially seeing 3 cases in just 20,000 people in the Pfizer study.
In the GSK study there was 1 case of GBS, and 2 cases of a kind of encephalitis called ADEM (acute disseminated encephalomyelitis). But reading through the fine details of the study, the 2 cases of ADEM were odd. They both occurred in 71 year-olds who received flu shots at the same time as the RSV jab. Furthermore, the ADEM diagnoses were based only on a doctor’s diagnosis, with no brain imaging or spinal tap performed. One of these ADEM cases was fatal, but in the final analysis the cause of death was revised to “dementia and hypoglycemia.” It was still included in the final analysis as ADEM though.
I wondered, do people over age 80 develop GBS more often than the background rate of 1-3 per 100,000? But I found a good meta-analysis that showed it’s truly around 3.
The truth about this GBS signal will be more clear with post-marketing surveillance that will be conducted by Pfizer and GSK. Hopefully GBS rates are not as high as 15 per 100,000 with vaccination. We just don’t know.
Also we need to watch for a slight increase in atrial fibrillation. This abnormal heart rhythm was reported in 10 participants who received GSK’s Arexvy and 4 participants who received a placebo. If I recall correctly, several of the patients had experienced atrial fibrillation episodes prior to vaccination, so this could have been more of a recurrence being triggered, albeit rarely.
~ Where can I get the RSV vaccine?
From what I’ve read, and from what I’ve learned from a few calls with local pharmacists, these shots will be covered by Medicare under the Part D benefit. This means that doctors’ offices will probably not be stocking these vaccines, as Medicare Part D does not reimburse our costs! And these shots cost hundreds of dollars, plus a small administration fee at the pharmacy. Many pharmacies already have them.
~ If I’m going to get the vaccine, when should I go for it?
Typically RSV season is after the holidays in winter, but last year it started early. Peak hospitalizations occurred for the littlest ones in November, with up to 250 out of every 100,000 babies being hospitalized. That is actually a staggeringly high rate compared to usual years. For those over age 85 years of age, the CDC reported a peak in December, with a maximum rate of 16 hospitalizations per 100,000 people. I learned this from a fascinating interactive dashboard/graph maintained by the CDC.
Anyway, it looks like these RSV shots are durable for months, but do taper downwards about 6-8 months in. If you’re going to get the vaccine, it’s probably best to just go for it within the next month or so. According to Dr. Leana Wen in an article from The Washington Post:
The RSV vaccine appears to have good durability, lasting at least eight months. RSV typically surges in late fall and winter, though as we saw last year, it could begin as early as the end of August. This makes timing for the RSV vaccine easy: Older adults should get it as soon as it’s available because it will last throughout the winter.
~Why rush to get the RSV vaccine with the flu shot, or another vaccine at the same time?
Some research suggests that receiving the RSV and flu shot together produces lower levels of antibodies than when delivered one at a time. There’s also potential for more symptoms after the simultaneous jabs. For example, a study last year showed that adults who got both the flu shot and the Covid booster at the same time had more side effects at least 10% of the time.
Ideally people should get their flu shots by the end of October, so no rush to get one in August.
I like to space any needed shots by at least 2 weeks if I can, but for others the logistics of getting out for a second jab may be challenging. But as noted above, the two cases of ADEM in the GSK study both received a flu shot concomitantly. I don’t know why this would happen in a clinical trial.
It’s also important to consider the intuitive benefits of the RSV vaccine beyond the individual. More seniors vaccinated should reduce transmission of RSV between friends, family, and the littlest ones. For grandparents with grandchildren on the way soon, or already here but less than 1-2 years old, getting the RSV vaccine might help create a little firewall similar to the Tdap boost already recommended to reduce pertussis/whooping cough transmission from close family members.
~ Low tech prevention
Good ventilation and all the respiratory skills we learned with Covid will definitely help reduce risk of contracting RSV. It’s not airborne in the same way, and masks (especially N95/KN95) should work very well in crowded situation like planes, theaters, etc. Hand washing is important for preventing RSV, too. These methods work regardless of political affiliation.
The Respiratory Syncytial Virus (RSV) generally causes cold-like symptoms but can be more severe in vulnerable populations like the elderly and those over age 60 with chronic illnesses. Babies are at higher risk too, but have a different treatment and prevention strategy not described herein. The CDC recommends RSV vaccination for individuals over 60 after shared decision-making. Two vaccines, Pfizer's Abrysvo and GSK's Arexvy, have shown similar efficacy in preventing RSV-associated respiratory illnesses, with upwards of 80-90% effectiveness. While the relative risk reductions are indeed impressive, the absolute risk reductions are less eye popping, with high numbers needed to treat. Both vaccines have yet to prove effectiveness in reducing hospitalizations or deaths but are likely to do so when given to a larger population than the 25,000-30,000 studied. Concerns arise regarding neurological side effects, like Guillain-Barré syndrome, with a few cases observed, and possible rare triggering of atrial fibrillation. We won’t have very robust safety data until next year when post-marketing surveillance of this year’s results is completed. Yet overall, they seem pretty safe. The vaccines are durable through the 1-2 seasons studied but do wane a little each month. RSV season can start early as we saw last year.
And hopefully this post used maximum political restraint, validating concerns but reviewing benefits!
And by way of a disclaimer, please do not take this post as actual, individual advice! Like the CDC said, this vaccine is all about shared decision making between you and your provider in real life, real time, hashing it out. The content here is for pregaming that discussion only, and is hopefully in line with this statement from the CDC:
As part of this discussion, providers and patients should consider the patient’s risk for severe RSV-associated disease. Epidemiologic evidence indicates that persons aged ≥60 years who are at highest risk for severe RSV disease and who might be most likely to benefit from vaccination include those with chronic medical conditions such as lung diseases, including chronic obstructive pulmonary disease and asthma; cardiovascular diseases such as congestive heart failure and coronary artery disease; moderate or severe immune compromise (either attributable to a medical condition or receipt of immunosuppressive medications or treatment); diabetes mellitus; neurologic or neuromuscular conditions; kidney disorders, liver disorders, and hematologic disorders; persons who are frail; persons of advanced age; and persons with other underlying conditions or factors that the provider determines might increase the risk for severe RSV-associated respiratory disease (Box).
Adults aged ≥60 years who are residents of nursing homes and other long-term care facilities are also at risk for severe RSV disease. It should be noted that the numbers of persons enrolled in the trials who were frail, were of advanced age, and lived in long-term care facilities were limited, and persons with compromised immunity were excluded (some of whom might have an attenuated immune response to RSV vaccination). However, adults aged ≥60 years in these populations may receive vaccination using shared clinical decision-making given the potential for benefit.
~ Take good care, and I would love to hear your thoughts, considerations from other sources, and eventual experiences.